Improvement of Spastic Stroke Hemiparesis Using rTMS Combined with Motor Training

  • Satoko Koganemaru
  • Tatsuya Mima
  • Hidenao Fukuyama
  • Kazuhisa Domen
Conference paper


Stroke is the second most common cause of death and the leading cause of chronic disability in adults worldwide. Patients with chronic stroke often show increased flexor hypertonia in their affected upper limbs. Although an intervention strategy targeting the extensors of the affected upper limb might thus be expected to have benefits for functional recovery, conventional repetitive motor training has limited clinical ­utility. Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) could induce motor recovery. Therefore, we developed a new hybrid rehabilitation comprised of rTMS and motor training of the extensors in order to counteract flexor hypertonia. Five hertz rTMS of the upper-limb area of the primary motor cortex (M1), combined with extensor motor training, had a greater effect on motor recovery than either intervention alone in chronic stroke hemi­paresis. It resulted in an improvement of extensor movement and grip power, along with a reduction of flexor hypertonia in their paretic upper limbs. In addition, we found the long-lasting effect for more than 2 weeks, by repeating the hyprid rehabilitation 12 times in patients for 6 weeks. These findings indicate that this method can facilitate use-dependent plasticity and achieve functional recovery of motor impairments. This new hybrid form of rehabilitation could be a powerful rehabilitative approach for patients with hemiparetic stroke.


Transcranial Magnetic Stimulation Anodal tDCS Grip Power Motor Training Extensor Digitorum Communis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Feigin V, Anderson N, Gunn A, Rodgers A, Anderson C (2003) The emerging role of therapeutic hypothermia in acute stroke. Lancet Neurol 2:529PubMedCrossRefGoogle Scholar
  2. 2.
    Di Filippo M, Tozzi A, Costa C, Belcastro V, Tantucci M, Picconi B, Calabresi P (2008) Plasticity and repair in the post-ischemic brain. Neuropharmacology 55:353–362PubMedCrossRefGoogle Scholar
  3. 3.
    Trompetto C, Assini A, Buccolieri A, Marchese R, Abbruzzese G (2000) Motor recovery following stroke: a transcranial magnetic stimulation study. Clin Neurophysiol 111:1860–1867PubMedCrossRefGoogle Scholar
  4. 4.
    Ward NS, Brown MM, Thompson AJ, Frackowiak RS (2003) Neural correlates of motor recovery after stroke: a longitudinal fMRI study. Brain 126:2476–2496PubMedCrossRefGoogle Scholar
  5. 5.
    Ito U, Kawakami E, Nagasao J, Kuroiwa T, Nakano I, Oyanagi K (2006) Restitution of ­ischemic injuries in penumbra of cerebral cortex after temporary ischemia. Acta Neurochir Suppl 96:239–243PubMedCrossRefGoogle Scholar
  6. 6.
    Ito U, Kuroiwa T, Nagasao J, Kawakami E, Oyanagi K (2006) Temporal profiles of axon terminals, synapses and spines in the ischemic penumbra of the cerebral cortex: ultrastructure of neuronal remodeling. Stroke 37:2134–2139PubMedCrossRefGoogle Scholar
  7. 7.
    Rossini PM, Calautti C, Pauri F, Baron JC (2003) Post-stroke plastic reorganisation in the adult brain. Lancet Neurol 2:493–502PubMedCrossRefGoogle Scholar
  8. 8.
    Nudo RJ, Wise BM, SiFuentes F, Milliken GW (1996) Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science 272:1791–1794PubMedCrossRefGoogle Scholar
  9. 9.
    Duncan P, Studenski S, Richards L, Gollub S, Lai SM, Reker D, Perera S, Yates J, Koch V, Rigler S, Johnson D (2003) Randomized clinical trial of therapeutic exercise in subacute stroke. Stroke 34:2173–2180PubMedCrossRefGoogle Scholar
  10. 10.
    Nakayama H, Jorgensen HS, Raaschou HO, Olsen TS (1994) Recovery of upper extremity function in stroke patients: the Copenhagen stroke study. Arch Phys Med Rehabil 75:394–398PubMedCrossRefGoogle Scholar
  11. 11.
    Verheyden G, Nieuwboer A, De Wit L, Thijs V, Dobbelaere J, Devos H, Severijns D, Vanbeveren S, De Weerdt W (2008) Time course of trunk, arm, leg, and functional recovery after ischemic stroke. Neurorehabil Neural Repair 22:173–179PubMedGoogle Scholar
  12. 12.
    Hummel FC, Cohen LG (2005) Drivers of brain plasticity. Curr Opin Neurol 18:667–674PubMedCrossRefGoogle Scholar
  13. 13.
    Taub E (1980) Somatosensory deafferentiation research with monkeys: implications for rehabilitation medicine. In: Ince LP (ed) Behavioral psychology in rehabilitation medicine: clinical applications. Williams & Wilkins, New YorkGoogle Scholar
  14. 14.
    Taub E, Miller NE, Novack TA, Cook Iii EW, Fleming WC, Nepomuceno CS, Connell JS, Crago JE (1993) Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehabil 74:347–354PubMedGoogle Scholar
  15. 15.
    Wolf SL, Lecraw E, Barton LA, Jann BB (1989) Forced use of hemiplegic upper extremities to reverse the effect of learned nonuse among chronic stroke and head-injured patients. Exp Neurol 104:125–132PubMedCrossRefGoogle Scholar
  16. 16.
    Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D, Giuliani C, Light KE, Nichols-Larsen D (2006) Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA 296:2095–2104PubMedCrossRefGoogle Scholar
  17. 17.
    Dong Y, Dobkin BH, Cen SY, Wu AD, Winstein CJ (2006) Motor cortex activation during treatment may predict therapeutic gains in paretic hand function after stroke. Stroke 37:1552–1555PubMedCrossRefGoogle Scholar
  18. 18.
    Gauthier LV, Taub E, Perkins C, Ortmann M, Mark VW, Uswatte G (2008) Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke * supplemental material. Stroke 39:1520–1525PubMedCrossRefGoogle Scholar
  19. 19.
    Liepert J, Miltner WH, Bauder H, Sommer M, Dettmers C, Taub E, Weiller C (1998) Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett 250:5–8PubMedCrossRefGoogle Scholar
  20. 20.
    Khedr EM, Ahmed MA, Fathy N, Rothwell JC (2005) Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology 65:466–468PubMedCrossRefGoogle Scholar
  21. 21.
    Kim YH, You SH, Ko MH, Park JW, Lee KH, Jang SH, Yoo WK, Hallett M (2006) Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke 37:1471–1476PubMedCrossRefGoogle Scholar
  22. 22.
    Hummel F, Celnik P, Giraux P, Floel A, Wu W-H, Gerloff C, Cohen LG (2005) Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 128:490–499PubMedCrossRefGoogle Scholar
  23. 23.
    Mansur CG, Fregni F, Boggio PS, Riberto M, Gallucci-Neto J, Santos CM, Wagner T, Rigonatti SP, Marcolin MA, Pascual-Leone A (2005) A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology 64:1802–1804PubMedCrossRefGoogle Scholar
  24. 24.
    Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K (2005) Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke 36:2681–2686PubMedCrossRefGoogle Scholar
  25. 25.
    Fregni F, Boggio PS, Valle AC, Rocha RR, Duarte J, Ferreira MJ, Wagner T, Fecteau S, Rigonatti SP, Riberto M, Freedman SD, Pascual-Leone A (2006) A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke 37:2115–2122PubMedCrossRefGoogle Scholar
  26. 26.
    Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F (2007) Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci 25:123–129PubMedGoogle Scholar
  27. 27.
    Cardenas-Morales L, Nowak DA, Kammer T, Wolf RC, Schonfeldt-Lecuona C (2010) Mechanisms and applications of theta-burst rTMS on the human motor cortex. Brain Topogr 22:294–306PubMedCrossRefGoogle Scholar
  28. 28.
    Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206PubMedCrossRefGoogle Scholar
  29. 29.
    Talelli P, Greenwood RJ, Rothwell JC (2007) Exploring theta burst stimulation as an intervention to improve motor recovery in chronic stroke. Clin Neurophysiol 118:333–342PubMedCrossRefGoogle Scholar
  30. 30.
    Lomarev MP, Kim DY, Richardson SP, Voller B, Hallett M (2007) Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke. Clin Neurophysiol 118:2072–2075PubMedCrossRefGoogle Scholar
  31. 31.
    Butefisch CM, Davis BC, Sawaki L, Waldvogel D, Classen J, Kopylev L, Cohen LG (2002) Modulation of use-dependent plasticity by d-amphetamine. Ann Neurol 51:59–68PubMedCrossRefGoogle Scholar
  32. 32.
    Butefisch CM, Davis BC, Wise SP, Sawaki L, Kopylev L, Classen J, Cohen LG (2000) Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci USA 97:3661–3665PubMedCrossRefGoogle Scholar
  33. 33.
    Trombly CA, Thayer-Nason L, Bliss G, Girard CA, Lyrist LA, Brexa-Hooson A (1986) The effectiveness of therapy in improving finger extension in stroke patients. Am J Occup Ther 40:612–617PubMedCrossRefGoogle Scholar
  34. 34.
    Koganemaru S, Mima T, Thabit MN, Ikkaku T, Shimada K, Kanematsu M, Takahashi K, Fawi G, Takahashi R, Fukuyama H, Domen K (2010) Recovery of upper-limb function due to enhanced use-dependent plasticity in chronic stroke patients. Brain 133:3373–3384PubMedCrossRefGoogle Scholar
  35. 35.
    Ashworth B (1964) Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 192:540–543PubMedGoogle Scholar
  36. 36.
    Bohannon RW, Smith MB (1987) Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67:206–207PubMedGoogle Scholar
  37. 37.
    Georgopoulos AP, Kalaska JF, Caminiti R, Massey JT (1982) On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex. J Neurosci 2:1527–1537PubMedGoogle Scholar
  38. 38.
    Kakei S, Hoffman DS, Strick PL (2001) Direction of action is represented in the ventral premotor cortex. Nat Neurosci 4:1020–1025PubMedCrossRefGoogle Scholar
  39. 39.
    Muir RB, Lemon RN (1983) Corticospinal neurons with a special role in precision grip. Brain Res 261:312–316PubMedCrossRefGoogle Scholar
  40. 40.
    Rizzolatti G, Fadiga L, Gallese V, Fogassi L (1996) Premotor cortex and the recognition of motor actions. Brain Res Cogn Brain Res 3:131–141PubMedCrossRefGoogle Scholar
  41. 41.
    Akeson WH, Woo SL, Amiel D, Matthews JV (1974) Biomechanical and biochemical changes in the periarticular connective tissue during contracture development in the immobilized rabbit knee. Connect Tissue Res 2:315–323PubMedCrossRefGoogle Scholar
  42. 42.
    Dietz V, Ketelsen UP, Berger W, Quintern J (1986) Motor unit involvement in spastic paresis. Relationship between leg muscle activation and histochemistry. J Neurol Sci 75:89–103PubMedCrossRefGoogle Scholar
  43. 43.
    Edstrom L (1970) Selective changes in the sizes of red and white muscle fibres in upper motor lesions and Parkinsonism. J Neurol Sci 11:537–550PubMedCrossRefGoogle Scholar
  44. 44.
    Goldspink G, Tabary C, Tabary JC, Tardieu C, Tardieu G (1974) Effect of denervation on the adaptation of sarcomere number and muscle extensibility to the functional length of the muscle. J Physiol 236:733–742PubMedGoogle Scholar
  45. 45.
    Hachinski V, Donnan GA, Gorelick PB, Hacke W, Cramer SC, Kaste M, Fisher M, Brainin M, Buchan AM, Lo EH, Skolnick BE, Furie KL, Hankey GJ, Kivipelto M, Morris J, Rothwell PM, Sacco RL, Smith SC Jr, Wang Y, Bryer A, Ford GA, Iadecola C, Martins SCO, Saver J, Skvortsova V, Bayley M, Bednar MM, Duncan P, Enney L, Finklestein S, Jones TA, Kalra L, Kleim J, Nitkin R, Teasell R, Weiller C, Desai B, Goldberg MP, Heiss W-D, Saarelma O, Schwamm LH, Shinohara Y, Trivedi B, Wahlgren N, Wong LK, Hakim A, Norrving B, Prudhomme S, Bornstein NM, Davis SM, Goldstein LB, Leys D, Tuomilehto J (2010) Stroke: working toward a prioritized world agenda. Stroke 41:1084–1099PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Human Brain Research CenterKyoto University School of MedicineSakyo-kuJapan
  2. 2.Department of Physical and Rehabilitation MedicineHyogo College of MedicineNishinomiyaJapan

Personalised recommendations